Tolylboronic acid → 3-Cyano-4-(4-tolyl)pyridine

Participants

Reaction Steps

Synthetic Scheme XXVII shows the 5-step preparation of the alkylating reagent 4-(4-bromomethylphenyl)-3-cyanopyridine (69) from 4-bromopyridine (70) (Aldrich). In step 1, the ortho-bromo carbanion was generated with LDA in THF at -78° C. and reacted with anhydrous DMF to give the 4-bromo-3-carboxaldehyde 71. In step 2, the aldehyde 71 was reacted with hydroxylamine to give the oxime 72. In step 3, the oxime 72 was dehydrated with 1,1-carbonyldiimidazole in methylene chloride at reflux to give 4-bromo-3-cyanopyridine (73). In step 4, the nitrile 73 was coupled with 4-methylphenylboronic acid (52) (Scheme XXIV) using Snieckus conditions (Scheme XIII) to give 3-cyano-4-(4-methylphenyl)pridine (74). In step 5, 74 was brominated with NBS/AIBN in carbon tetrachloride at reflux to give the desired alkylating reagent 69. ##STR81##

Provenance & Evidence